Our objective is to determine whether liver fatty acid binding protein (L-FABP) and a closely related protein act as cytoplasmic receptors of growth-promoting fatty acid metabolites and ultimate carcinogens in rat hepatocytes. We have assembled a body of evidence in support of our proposal that L-FABP contains ligands that promote growth in normal, pre- malignant and malignant hepatocytes in rats. In addition, L-FABP is the principal protein target of the liver carcinogen, N-2- acetylaminofluorene (2-acetylaminofluorene), during early stages of carcinogenesis. We will study ligands of liver fatty acid binding protein and a related polypeptide both in vitro and in normal and carcinogen-altered hepatocytes of rats, as follows: Project I: Ligands of L-FABP 1. In vitro dissociable ligands of L-FABP 2. In vivo dissociable ligands of L-FABP 3. Competition between normal ligands and activated carcinogen Project II: Cloning, Ligand-Binding and Cellular Levels of a Protein Related to L-FABP 1. cDNA cloning, nucleotide sequence and identification 2. In vitro dissociable ligands 3. Level of regulation 4. Tissue levels